1. Field of the Invention
This invention relates to hemodialysis and peritoneal dialysis.
More particularly, this invention relates to: (a) dry, free-flowing, stable, dust-free, non-caking, granular products or compositions which are readily soluble in water and which are suitable and useful for preparing solutions for use in hemodialysers and in peritoneal dialysis and (b) to the preparation of such granular products.
2. Description of the Prior Art
Hemodialysers, which are known as "artificial kidneys" and which are also referred to as "dialysers", are used in the care of patients suffering from renal deficiencies because of disease or injury. Such devices remove waste matter (waste products of metabolism) from blood by means of a semipermeable membrane and a specially formulated solution which extracts the wast matter through the semi-permeable membrane. In hemodialysis, blood is removed from a patient's body and circulated through a dialyser to remove waste products from the blood. On the other hand, in peritoneal dialysis, a dialysis solution is injected into the patient's abdominal cavity where wastes pass through the membranes of the patient's body into the dialysis solution which is subsequently drained from the abdominal cavity.
Solutions used in hemodialysers or in peritoneal dialysis generally contain, as major components, dextrose (if required by the patient), sodium chloride and sodium acetate and/or sodium bicarbonate (the sodium acetate or sodium bicarbonate serves as an alkalizing agent), along with smaller amounts of calcium, magnesium and sometimes potassium as chlorides and other water soluble physiologically acceptable salts, such as small amounts of lactates or gluconates if required by the patient. These materials (e.g., lactates and gluconates) must not be present in amounts sufficient to precipitate calcium or magnesium ions. Potassium acetate and gluconates and lactates of sodium, potassium, magnesium or calcium, if present, also serve as alkalizing agents.
Peritoneal dialysis is described in the June 2, 1980 issue of Barrons at pages 35 and 42.
To date, commercial practice has been largely limited to supplying hemodialysis and peritoneal dialysis solutions in the form of liquid concentrates, although it has been recognized for years that a stable dry product capable of being readily and completely dissolved in water would have convenience and handling cost advantages. Such a dry product is taught by U.S. Pat. No. 3,560,380. Products described therein are made by combining a specially prepared spray-dried sodium acetate, having a moisture content of less than 0.2% by weight, with ordinary anhydrous grades of other materials to form a simple physical mixture. A further provision is that the total moisture content of the composition does not exceed 0.75%. Product stability against caking and discoloration is said to result from the low water content of the spray-dried sodium acetate. Such products have not obtained broad acceptance in the marketplace, possibly because of the small particle size of the spray-dried materials. Spray-dried sodium acetate is dusty and, consequently, has unpleasant handling characteristics.
A prior art dialysis solution based on bicarbonate is described in a bulletin entitled "SB-600 Bicarbonate Batch Formula", published by Renal Systems, Inc., 14905 28th Ave. North, Minneapolis, Minn. 55441. The precursor of said solution is provided in two parts. These are (a) a first part comprising 3.42 liters of an "acid based concentrate", and (b) a second part which is 393 g of sodium bicarbonate. The first part is diluted to slightly less than 120 liters with water, the second part (the sodium bicarbonate) is admixed in approximately one quart of water and added to the aforesaid diluted first part. The resulting mixture is diluted with water to 120 liters to form a bicarbonate based dialysis solution which will be referred to as "Solution A". Said Solution A contains:
______________________________________ MEq/l Eq/l gms/l ______________________________________ Sodium 140 or 0.140 or 0.14 .times. 23 = 3.22 Calcium 3.5 or 0.0035 ##STR1## = 0.0701 Magnesium 1.5 or 0.0015 ##STR2## = 0.0182 Chloride 106 or 0.106 or 0.106 .times. 35.45 = 3.7577 Bicarbonate 35 or 0.035 or 0.035 .times. 61 = 2.1350 Dextrose 250 or 0.250 or 0.250 .times. 180 = 45.0 (C.sub.6 H.sub.12 O.sub.6) ______________________________________
As noted supra, in the above Renal Systems SB-600 Bicarbonate Batch Formula, all constituents except the sodium bicarbonate are contained in the acid based concentrate as sodium chloride, calcium chloride, magnesium chloride and dextrose.
Other chemicals (e.g., potassium chloride), if required, are added and, if necessary, the pH is adjusted to 7.2 to 7.4 after mixing the acid based concentrate and the sodium bicarbonate but before using the resulting solution.
It should be noted that the use of sodium bicarbonate comprising dialysate solutions is complicated by the fact that calcium and magnesium ions do not remain soluble in the presence of concentrated sodium bicarbonate solutions. In the presence of water, calcium and magnesium ions tend to combine with carbonate present and readily precipitate at low concentrations. pH must be closely controlled.
In the early 1960s (Mion, C. M. et al, "Substitution of Sodium Acetate for Sodium Bicarbonate in the Bath Fluid for Hemodialysis", Trans. Am. Soc. Artif. Internal Organs 10:110, 1964), sodium acetate was instituted for sodium bicarbonate as the fixed base in hemodialysis solutions. This was done primarily because the sodium acetate containing solutions were more stable in use, whereas the sodium bicarbonate comprising solutions were less stable because of the low solubility of calcium and magnesium carbonates. It is essential that exact control of various necessary ions in the dialysis solution be obtained. The tendency for calcium and magnesium carbonates to precipitate at solution use concentrations caused the switch in 1964 from sodium bicarbonate as the fixed base to sodium acetate. This switch also made possible the use of proportioning pumps to handle dialysate concentrates.
Information is now surfacing indicating that there is "Less Dialysis-Induced Morbidity and Vascular Instability with Bicarbonate in Dialysate" (U. Graefe et al, March, 1978, Annals of Internal Medicine, Vol. 88, No. 3, pages 332-336). It is now evident that bicarbonate in a dialysate solution, rather than acetate, is better tolerated by the patient.